决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:CD58 could be a leukemic marker in patients with relapsed/refractory B-cell acute lymphoblastic leukemia after multiline therapies.
CD58 could be a leukemic marker in patients with relapsed/refractory B-cell acute lymphoblastic leukemia after multiline therapies.
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CD58 抗原在经多线治疗(包括 allo-HCT 和 CAR-T)后的 r/r B-ALL 患者中稳定表达,提示其在重度治疗患者中仍可作为白血病标志物。
作为B细胞急性淋巴细胞白血病(B-ALL)微小残留病标志物,CD58已在初诊患者及标准化疗后短期随访患者中得到报道。但对于接受长期、多线治疗(尤其CAR-T 细胞治疗)的复发/难治(r/r)患者,目前尚无相关数据。本研究重点调查此类患者的CD58状态。
采用多参数流式细胞术检测淋巴母细胞的CD58表达;评估CAR-T 治疗前以及CAR-T 治疗失败或复发患者的CD58状态。
在274例尚未接受CAR-T 细胞治疗的儿童及成人患者中(22.3%曾接受异基因造血细胞移植[allo-HCT]),228例(83.2%)CD58阳性。此外,在CAR-T 治疗前CD58阳性、随后治疗失败或复发的58例患者中(半数在CD19 CAR-T 后还接受了CD22 CAR-T 或allo-HCT巩固治疗),全体患者的CD58表达率为79.3%(46/58);仅接受CD19 CAR-T 治疗者为86.2%(25/29)。
在包括allo-HCT和CAR-T 在内的多线治疗后,r/r B-ALL患者仍稳定表达CD58,提示即使在接受多次治疗的患者中,CD58仍可作为白血病标志物。
As a marker of minimal residual disease in B-cell acute lymphoblastic leukemia (B-ALL), CD58 has been reported in B-ALL at diagnosis and short-term follow-ups after standard chemotherapies. However, there are no data available in relapsed/refractory (r/r) patients who have received long-term and multiline therapies, especially chimeric antigen receptor (CAR) T cells; here, we focused on investigating CD58 status in these patients.
CD58 expression on lymphoblasts was detected by multiparameter flow cytometry. CD58 status was evaluated in patients with r/r B-ALL before CAR-T therapy, and the patients who failed or relapsed after CAR-T.
Among 274 pediatric and adult patients prior to exposure to CAR-T cells (22.3% of them underwent allogeneic hematopoietic cell transplantation, allo-HCT), 228 (83.2%) showed CD58 positivity. Furthermore, among 58 patients who were CD58 positive before CAR-T failed or relapsed after CAR-T (half also received CD22 CAR-T or allo-HCT as a consolidation treatment following CD19 CAR-T), the frequency of CD58 expression was 79.3% (46/58) in all patients and 86.2% (25/29) in patients exposed to CD19 CAR-T cells alone.
CD58 antigen was stably expressed in patients with r/r B-ALL after multiline therapies, including allo-HCT and CAR-T, indicating that it could still be a leukemic marker in heavily treated patients.
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